Int J Biol Sci 2014; 10(7):777-788. doi:10.7150/ijbs.9220
A Novel Role of Exogenous Carbon Monoxide on Protecting Cardiac Function and Improving Survival against Sepsis via Mitochondrial Energetic Metabolism Pathway
Department of Burn and Plastic Surgery, Affiliated Hospital, Jiangsu University, Zhenjiang, Jiangsu Province, China
* These authors contributed equally to this work.
Septic cardiac dysfunction is the main cause of death in septic patients. Here we investigate whether exogenous carbon monoxide can protect cardiac function and improve survival against sepsis by interfering with mitochondrial energetic metabolism. Male C57BL/6 mice were subjected to cecal ligation and puncture to induce sepsis. Exogenous carbon monoxide delivered from Tricarbonyldichlororuthenium (II) dimer (carbon monoxide releasing molecule II, 8mg/kg) was used intravenously as intervention. We found that carbon monoxide significantly improved cardiac function (LVEF 80.26 ± 2.37% vs. 71.21 ± 1.37%, P < 0.001; LVFS 43.52 ± 1.92% vs. 34.93 ± 1.28%, P < 0.001) and increased survival rate of septic mice (63% vs. 25%, P < 0.01). This phenomenon might be owing to the beneficial effect of carbon monoxide on abolishing the elevation of cardiac enzyme activity, cytokines levels and apoptosis rate, then attenuating cardiac injury in septic mice. Meanwhile, carbon monoxide significantly reversed the loss of mitochondrial number, effectively inhibited cardiac mitochondrial damage in septic mice by modulating glucose uptake, adenosine triphosphate and lactate content. Furthermore upregulation of peroxisome proliferator-activated receptor-γ coactivator-1α, nuclear respiratory factor 1 and mitochondrial transcription factor A genes in cardiac tissue were revealed in septic mice treated with carbon monoxide. Taken together, the results indicate that exogenous carbon monoxide effectively modulated mitochondrial energetic metabolisms by interfering with expression of peroxisome proliferator-activated receptor-γ coactivator-1α, nuclear respiratory factor 1 and mitochondrial transcription factor A genes, consequently exerted an important improvement in sepsis-induced cardiac dysfunction.
Keywords: Sepsis, Cardiac function, Carbon monoxide, Energy metabolism, Gene expression
Wang X, Qin W, Qiu X, Cao J, Liu D, Sun B. A Novel Role of Exogenous Carbon Monoxide on Protecting Cardiac Function and Improving Survival against Sepsis via Mitochondrial Energetic Metabolism Pathway. Int J Biol Sci 2014; 10(7):777-788. doi:10.7150/ijbs.9220. Available from http://www.ijbs.com/v10p0777.htm